Histocompatibility genes, mapping to the major histocompatibility complex (MHC), code for cell membrane components which play a prominent role in the regulation of the immune response. MHC genes regulate lymphocyte collaboration, antigen presentation to effector lymphocytes, immune responsiveness, and susceptibility to neoplastic and immune diseases. The vast majority of information on the immunological function of the MHC has been obtained in the mouse MHC (H-2). Analyses of mouse and human MHC's have suggested that MHC's in different species may possess unique characteristics despite unifying similarities. Therefore, caution should be exercised in offering generalities about MHC organization and function based on observatons from a limited number of species. The major efforts of this research are concerned with the comprehensive anslysis of the rat MHC, RT1. Emphasis will be placed on the following studies: (1) serological and biochemical characterization of rat Class II (Ia) antigens with the intention of elucidating the extent of polymorphism at the two Class II loci in the rat, (2) identification of intra-RT1 recombinants in order to delineate the RT1 linkage map, and (3) identification of previously undiscovered RT1 genes. The proposed studies will have a major impact on the knowledge of the genetic organization of rat MHC genes, the molecular characteristics of their products, and their immunological function.